1. Field of the Invention
This invention relates to novel benzoic acid derivative compounds, and more particularly to novel benzoic acid derivatives and pharmaceutical compositions suitable for use as anti-inflammatory agents.
2. Description of the Prior Art
The treatment of inflammatory conditions, such as atopic dermatitis, contact dermatitis, psoriasis, rheumatoid arthritis, glomerulonephritis, osteoarthritis, lupus erythematosus, scleroderma, asthma and irritable bowel disease has in the past involved the use of agents such as aspirin-like nonsteroidal anti-inflammatory agents, glucocorticoids, methotrexate and cyclophosphamide. Unfortunately, these agents generally produce unwanted side effects.
Nonsteroidal anti-inflammatory drugs (NSADs), while reducing inflammatory symptoms, do not prevent progression of disease and have serious side effects, including gastric ulceration. Glucocorticosteroids provide dramatic relief in some diseases but with systemic side effects which often preclude chronic use at efficacious doses. Furthermore, certain cytotoxic agents can provide substantial relief, but elicit major toxicity. Methotrexate has been associated with patient death. Cyclophosphamide has carcinogenic liability. Thus, new agents for treating inflammatory conditions that are free of these adverse side effects are needed.
Burch et al. in "N-(Fluorenyl-9-methoxycarbonyl)amino acids, a class of anti-inflammatory agents with a different mechanism of action", Proc. Natl. Acad. Sci, USA, (1991) 88:355-359, discloses several members of a series of (N-fluorenyl-9-methoxycarbonyl)amino acids as possessing a broad spectrum of anti-inflammatory activity. The compounds are disclosed as being active against oxazolone dermatitis in mice and adjuvant arthritis in rat models in which activated T-lymphocytes are implicated. Burch et al. found that the compounds also inhibited T-lympocyte activation in vitro, assessed by using the mixed lymphocyte reaction and that the compounds inhibited the reversed passive Arthus reaction in rats and arachidonic acid-induced dermatitis in mice models in which leukocyte infiltration is responsible for the inflammatory reaction.